We have a reproducible model of adoptive tumor immunity in which lymphoid cell subpopulations from tumor-bearing mice may be tested for their efficacy in the inhibition of tumor growth, and those tumor cells which survive this immunologic attack may be tested for protective alterations in their tumor specific transplantation antigens. Experimental procedures are proposed to further refine and define this assay system as to the composition of the responding cellular elements and their identity. The proposal will attempt to identify the lymphoid cell or cells which are able to inhibit tumor growth in vivo and to identify what, if any, lymphoid cell subpopulations are present which may regulate this protective response. When these experiments are completed the defined adoptive transfer model will be used to test the hypothesis of protective tumor cell antigenic adaptation. Experiments will be performed to test whether such an antigenic loss or change occurs and whether it is temporary or inheritable. Further experiments will be designed to assay the antigenic character of tumor cells which metastasize and determine whether certain antigenic changes are associated with metastasis to specific anatomic sites. Additionally, this proposal will attempt to study the relationship of tumor rejection antigens identified in tumor-free immunized animals to those in tumor-bearing animals. This proposal will attempt to study the adaptive response of the host immunologic system and the tumor cells to each other during the natural history of tumor-bearing. Knowledge of this adaptive interplay is fundamental to the design and understanding of future immunotherapeutic and combined immunotherapeutic and chemotherapeutic treatment of tumors.